The proposed work is directed toward an understanding of the structure of the mast cell granule and the mechanism of secretion. Histamine loading of granules will be studied using intact mast cells and mast cell granules isolated with and without their surrounding membranes. Binding of histamine to macromolecular heparin will be compared to histamine binding to granule matrices; the effect of the major mast cell protein on binding of histamine to heparin will also be examined. Studies on membrane events immediately preceding secretion will be carried out using fluorescent labels and energy transfer.